TANK potentiates tumor necrosis factor receptor-associated factor-mediatedc-Jun N-terminal kinase/stress-activated protein kinase activation throughthe germinal center kinase pathway

Tumor necrosis factor (TNF) receptor-associated factors (TRAFs) are mediato rs of many members of the TNF receptor superfamily and can activate both th e nuclear factor kappa B (NF-kappa B) and stress-activated protein kinase ( SAPK; also known as c-jun N-terminal kinase) signal transduction pathways. We previously described the involvement of a TRAF-interacting molecule, TRA F-associated NF-kappa B activator (TANK), in TRAF2-mediated NF-kappa B acti vation. Here we show that TANK synergized with TRAF2, TRAF5, and TRAF6 but not with TRAF3 in SAPK activation. TRAF2 and TANK individually formed weak interactions with germinal center kinase (GCK)-related kinase (GCKR). Howev er, when coexpressed, they formed a strong complex with GCKR, thereby provi ding a potential mechanism for TRAF and TANK synergy in GCKR-mediated SAPK activation, which is important in TNF family receptor signaling. Our result s also suggest that TANK can form potential intermolecular as well as intra molecular interactions between its amino terminus and carboxyl terminus. Th is study suggests that TANK is a regulatory molecule controlling the thresh old of NF-kappa B and SAPK activities in response to activation of TNF rece ptors. In addition, CD40 activated endogenous GCKR in primary B cells, impl icating GCK family proteins in CD40-mediated B-cell functions.